1. Filed of the Invention
The present invention relates to a ketosis-treating agent. Particularly, it relates to a ketosis-treating agent which shows little influence on glucose metabolism and/or has a long duration of its effect.
2. Brief Description of the Background Art
Mobilization of free fatty acids from fatty tissue increases at diabetes, starvation, physical exercise, external injury, surgical operation, attack of fever, or the like, so that fatty acid oxidation in the liver is accelerated because of decrease of utilization of sugars, deficiency of insulin, stress, and the like. As a result, formation of ketone bodies, which is the general term for acetoacetic acid, 3-hydroxybutyric acid and acetone, increases. When the formation of ketone bodies exceeds the capacity of treating it, the ketone bodies are accumulated in blood to cause ketonemia. Conditions where the concentration of ketone bodies is high in urine are called ketonuria, and both of them are called generally ketosis. Since acetoacetic acid and 3-hydroxybutyric acid are strong acids of a medium level, in the case where accumulation of ketone bodies exceeds the buffering capacity of a living body, metabolic acidosis is caused and the living body falls into a fatal state called ketoacidosis. For example, excessive formation of ketone bodies for a long period, of time such as diabetes causes ketoacidosis to finally result in death.
Generally, in order to prevent or treat ketosis, insulin or a sugar, such as glucose or the like, is administered. However, as discussed above, glucose metabolism is disordered in many cases of falling into ketosis so that there is a problem that a blood glucose value largely varies by such administration of insulin or a sugar.
Furthermore, in ruminants, as a result that 3-hydroxybutyric acid is formed from butyric acid that is a fermentation product in the digestive tract, the concentration of ketone bodies in blood even at a physiological state is higher than in non-ruminants, and therefore, the incidence of ketosis in ruminants is high. Especially in milk cows, excessive milk secretion causes imbalance of metabolism with improvement of the milk-secreting ability so that the incidence rate of ketosis is as high as about 10%. Moreover, there is a problem that subclinical ketosis, which does not show remarkable clinical symptoms but accompanies an increase of internal ketone bodies, is increasing and affects the milk secretion and the incidence of other metabolic diseases.
Ketosis is generally treated by intravenous administration of a solution of a sugar, such as glucose, xylitol, or the like, but the effect on reduction of the concentration of ketone bodies is transitory and lasts only a short period of time. Therefore, continuous intravenous injection is required. However, since intravenous administration for a long period of time is extremely difficult, there arises a problem that it is usually required to repeat such single administration frequently (Metabolic Diseases of Cattle (Usi no Taishasei Sikkan), Gakusosha, p. 36).
On the other hand, there are reports on the effects of alanine, aspartic acid and glutamine upon reduction of the concentration of ketone bodies in blood in vivo (Romano Nosadini, Biochem. J., 190:323-332 (1980); Eugenio Cersosimo, Am. J. Ohysiol., 250:E248-E252 (1986)). Especially, the mechanism of reducing ketone bodies in blood was precisely examined on alanine, and it is suggested that it inhibits the formation of acetoacetic acid from acetyl CoA produced by fatty acid oxidation. Furthermore, a similar mechanism has been considered for aspartic acid. However, in these amino acids, there also exists a problem that, in single administration, the effect on reduction of the concentration of ketone bodies is transitory and lasts only a short period of time. Also, as for glutamine, only action of reducing the concentration of ketone bodies at continuous administration was reported, but the presence of the effect on reduction of ketone bodies at single administration and the durability of the effect are not known.
An object of the present invention is to provide a ketosis-treating agent which does not increase a blood glucose value and shows extremely little influence on glucose metabolism, in view of the circumstances that there are many cases where glucose metabolism is disordered in a ketosis state as described above.
A further object of the present invention is to provide a ketosis-treating agent which does not require frequent administration and has long duration of the effect.
The present invention relates to a ketosis-treating agent comprising, as an active ingredient, at least one amino acid selected from valine, isoleucine, serine, glutamine and glutamic acid, or a peptide or protein comprising at least one amino acid selected from valine, isoleucine, serine, glutamine and glutamic acid.
Furthermore, the present invention relates to a method for treating or preventing ketosis, comprising administering to a human or animal an effective amount of the above agent.
Moreover, the present invention relates to a method for treating or preventing symptoms relating to ketone bodies, comprising administering to a human or animal an effective amount of the above agent.